tbuckley/cabot-search huggingface dataset:
P924: TREATMENT PATTERNS OF TRIPLE-CLASS REFRACTORY (TCR) MULTIPLE MYELOMA (MM) ACROSS THE UNITED STATES (US), CANADA, AND WESTERN EUROPE: A REAL-WORLD OBSERVATIONAL CHART REVIEW STUDY
Authors: Ravi K Goyal, Gaelle Frugier, Julien Rombi, Lizzi Esterberg, Keith Davis, Patrick Hlavacek, Jinma Ren, Alex Schepart, Didem Aydin, Marco Dibonaventura
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Most patients with MM eventually become refractory to the three main therapy classes used to treat the disease: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). Aims: The objective of the present study was to describe the management of patients who have become TCR and how treatment strategies vary across countries. Methods: A retrospective chart review study was conducted across the US, Canada (CA), the UK, France (FR), Germany (DE), Spain (ES), Belgium (BE), the Netherlands (NL), and Sweden (SE). Oncologists/hematologists were recruited to abstract medical chart information from eligible patients (eg, diagnosed with MM, clinician-reported refractoriness to ≥1 IMiD, ≥1 PI, and ≥1 anti-CD38 antibody treatment) into an electronic case report form. Patients had to initiate their first (index) therapy after becoming TCR between 11/1/2015 and 12/31/2019. Chart abstractions were performed from February through October 2022. Demographics, baseline clinical characteristics, and treatment patterns were descriptively analyzed. Results: A total of 718 patients with TCR MM were included (61.4% male; median age at index=64.2 years); 25.8% had an ECOG score of 2 and 28.7% had high cytogenetic risk [ie, t(4:14), t(14:16), and/or del(17p)]. Patients received a median of 3 treatment lines prior to their index therapy (19.4% were penta-exposed). In the post TCR setting, the most frequently used treatments included IMiDs (52.5%), PIs (40.8%), chemotherapy (CT; 27.3%), and mAbs (16.3%). Treatment class usage also varied significantly by country (Table 1). Summary/Conclusion: Our global chart review indicated that many patients reach TCR status after only a few lines of therapy and, after this point, retreating with IMiDs, PIs, and mAbs was common practice. The diversity of treatment classes used in this setting underscores the challenges across countries with managing a TCR population due to the lack of a clear standard of care.Keywords: Treatment, Multiple myeloma, Myeloma, Real world data
Efficiency Encapsulation of FK506 with New Dual Self‐Assembly Multi‐Hydrophobic‐Core Nanoparticles for Preventing Keratoplasty Rejection (Adv. Healthcare Mater. 21/2023)
Authors: Dongmei Wang, Baoshan Huang, Chenchen Zhu, Lei Wang, Jiahui Jin, Jingyang Tan, Qing Li, Shengjin Xiang, Kaihui Nan, Sen Lin
Journal: Advanced Healthcare Materials (2023)
Dual credit assignment processes underlie dopamine signals in a complex spatial environment
Authors: Timothy A. Krausz, Alison E. Comrie, Ari E. Kahn, Loren M. Frank, Nathaniel D. Daw, Joshua D. Berke
Journal: Neuron (2023)

Animals frequently make decisions based on expectations of future reward ("values"). Values are updated by ongoing experience: places and choices that result in reward are assigned greater value. Yet, the specific algorithms used by the brain for such credit assignment remain unclear. We monitored accumbens dopamine as rats foraged for rewards in a complex, changing environment. We observed brief dopamine pulses both at reward receipt (scaling with prediction error) and at novel path opportunities. Dopamine also ramped up as rats ran toward reward ports, in proportion to the value at each location. By examining the evolution of these dopamine place-value signals, we found evidence for two distinct update processes: progressive propagation of value along taken paths, as in temporal difference learning, and inference of value throughout the maze, using internal models. Our results demonstrate that within rich, naturalistic environments dopamine conveys place values that are updated via multiple, complementary learning algorithms.
Triacylglycerol uptake and handling by macrophages: From fatty acids to lipoproteins
Authors: Lei Deng, Sander Kersten, Rinke Stienstra
Journal: Progress in Lipid Research (2023)

Macrophages are essential innate immune cells and form our first line of immune defense. Also known as professional phagocytes, macrophages interact and take up various particles, including lipids. Defective lipid handling can drive excessive lipid accumulation leading to foam cell formation, a key feature of various cardiometabolic conditions such as atherosclerosis, non-alcoholic fatty liver disease, and obesity. At the same time, intracellular lipid storage and foam cell formation can also be viewed as a protective and anti-lipotoxic mechanism against a lipid-rich environment and associated elevated lipid uptake. Traditionally, foam cell formation has primarily been linked to cholesterol uptake via native and modified low-density lipoproteins. However, other lipids, including non-esterified fatty acids and triacylglycerol (TAG)-rich lipoproteins (very low-density lipoproteins and chylomicrons), can also interact with macrophages. Recent studies have identified multiple pathways mediating TAG uptake and processing by macrophages, including endocytosis and receptor/transporter-mediated internalization and transport. This review will present the current knowledge of how macrophages take up different lipids and lipoprotein particles and address how TAG-rich lipoproteins are processed intracellularly. Understanding how macrophages take up and process different lipid species such as TAG is necessary to design future therapeutic interventions to correct excessive lipid accumulation and associated co-morbidities.
P768: PRELIMINARY EXPLORATION ON LAG-3 EXPRESSION OF BONE MARROW-DERIVED MACROPHAGES IN SEVERE APLASTIC ANEMIA
Authors: Congwei Zhong, Xiaowei Liang, Chunyan Liu, Rong Fu
Journal: HemaSphere (2023)

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background: Hyperfunction of CTL is a key factor in the pathogenesis of severe aplastic anemia (SAA). As a kind of antigen-presenting cells, macrophages can present antigens to T cells and remove foreign bodies invading the body. Most studies have shown that the mechanism of Lymphocyte-activation-gene-3 (LAG-3) is that it binds to its ligands and plays an immunosuppressive role, including participation in T cell proliferation, activation and cytokine production. At present, the role of bone marrow-derived macrophages in SAA patients in the immune pathogenesis of SAA is not clear. Aims: To investigate the expression of LAG3 in bone marrow-derived macrophages of SAA patients and its correlation with disease immune status. Methods: Flow cytometry (FCM) was used to detect the expression of LAG3 in bone marrow-derived macrophages from 15 untreated SAA patients, 12 remission SAA patients and 12 healthy controls. And the expression levels of IL-2, IL-4, IL-6, IL-10, TNF- α and IFN- γ in bone marrow supernatant of untreated SAA patients were also detected by FCM. R language was used to analyze the correlation between LAG3 expression level and peripheral blood cells, bone marrow hematopoietic function, immune cells and related functional molecules in newly diagnosed SAA patients. Results: The expression of LAG-3 in bone marrow macrophages of untreated SAA patients was significantly higher than that in remission group and Healthy control group (P < 0.001). The expression of LAG-3 in bone marrow-derived macrophages of untreated SAA patients was negatively correlated with leukocyte count (r=-0.625), neutrophil absolute value (r=-0.546), platelet count (r=-0.516), reticulocyte percentage (r=-0.608)and bone marrow granulocyte percentage (r=-0.530) (P < 0.05), but positively correlated with bone marrow lymphoid percentage (r=0.532) (P < 0.05). Also, it has no significant correlation with erythrocyte count, hemoglobin content and the percentage of bone marrow erythroid. The expression of LAG-3 in bone marrow-derived macrophages of untreated SAA patients was negatively correlated with the expression levels of IL-2 (r=-0.517), IL-4 (r=-0.535), IL-6 (r=-0.581) and the proportion of CD3+T cells (r=-0.569), but positively correlated with t he proportion of CD16+CD56+ cells (r=0.660) (P < 0.01). There was no significant correlation with the expression levels of IL-10, TNF- α, IFN- γ. Summary/Conclusion: LAG-3 is related to the pathogenesis of SAA. It may be used as a negative immunomodulatory molecule to maintain immune homeostasis by inhibiting hyperfunctional immune cells and play a role in saving the pathogenesis of SAA. The specific role of bone marrow-derived macrophages in patients with SAA needs to be further explored.Keywords: Aplastic anemia, Macrophage
Antitumor immunity as the basis for durable disease-free treatment-free survival in patients with metastatic urothelial cancer
Authors: Jonathan Anker, Sumanta K Pal, Seunghee Kim-Schulze, Huan Wang, Rebecca Halperin, Andrew Uzilov, Naoko Imai, Shingo Eikawa, Takuro Saito, Robert Sebra, Noah M Hahn, Manishkumar Patel, Jingjing Qi, Hui Xie, Nina Bhardwaj, Sacha Gnjatic, Matthew D Galsky
Journal: Journal for ImmunoTherapy of Cancer (2023)

Cisplatin-based chemotherapy has been associated with durable disease control in a small subset of patients with metastatic urothelial cancer. However, the mechanistic basis for this phenomenon has remained elusive. Antitumor immunity may underlie these exceptional responders. In a phase II trial evaluating a phased schedule of gemcitabine and cisplatin followed by gemcitabine and cisplatin with ipilimumab for metastatic urothelial cancer, 4 of 36 patients achieved durable disease-free treatment-free survival (DDFTFS) and remain in remission over 5 years after enrolment on the study. We sought to identify the genomic and immunological mechanisms associated with functional cures of such patients. Whole exome sequencing was performed on pretreatment archival tumor tissue. Neoantigen prediction and ranking were performed using a novel pipeline. For a subset of patients with available biospecimens, selected peptides were tested for neoantigen-specific T cell reactivity in peripheral blood CD4
Neglible 10-year risk of liver-related events in chronic hepatitis B patients with low liver stiffness
Authors: Lesley Patmore, Kirsi van Eekhout, Ozgur Koc, Robert De Knegt, Bettina Hansen, Harry LA Janssen, Matthijs Kramer, Honkoop Pieter, Robert De Man, Bart Takkenberg, Milan Sonneveld
Journal: Journal of Hepatology (2023)
HBsAg induces mild activation, but not suppression, of intrahepatic immune cells as shown by single-cell RNA sequencing of fine-needle aspirates in chronic HBV patients
Authors: Zgjim Osmani, Boris Beudeker, Gertine Oord, Anthony Grooshuismink, Robert De Knegt, Eric Bindels, Harmen van de Werken, Andre Boonstra
Journal: Journal of Hepatology (2023)
Id-neoantigen vaccine induces therapeutic CD8<sup>+</sup>T cells against multiple myeloma: H chain-loss escapees cause FLC MM
Authors: Marita Westhrin, Jana Blazevski, Ana Textor, Pegah Abdollahi, Ramakrishna Prabhu Gopalakrishnan, Linda Thuy Ngo, Peter Olaf Hofgaard, Julia Heinzelbecker, Sonja Bobic, Even Fossum, Heidi Cecilie Larsen Spång, Ranveig Braathen, Bjarne Bogen
Journal: Journal for ImmunoTherapy of Cancer (2023)

Multiple myeloma (MM) cancers originate from plasma cells that have passed through the germinal center reaction where somatic hypermutation of Ig V regions takes place. Myeloma protein V regions often express many mutations and are thus a rich source of neoantigens (traditionally called idiotopes (Id)). Therefore, these are highly tumor-specific and excellent targets for immunotherapy. We have developed a DNA Id vaccine which as translated protein targets conventional dendritic cells (cDC) for CCL3-mediated delivery of myeloma protein V regions in a single-chain fragment variable (scFv) format. Vaccine efficacy was studied in the mouse MM model, mineral oil-induced plasmacytoma 315.BM. The Id vaccine protected mice against a challenge with MM cells. Moreover, the vaccine had a therapeutic effect. However, in some of the vaccinated mice, MM cells not producing H chains escaped rejection, resulting in free light chain (FLC) MM. Depletion of CD8+ T cells abrogated vaccine efficacy, and protection was observed to be dependent on cDC1s, using Batf3-/- mice. Modifications of scFv in the vaccine demonstrated that CD8+ T cells were specific for two mutated VH sequences. VH neoantigen-specific CD8+ T cells elicited by CCL3-containing Id vaccines had a therapeutic effect against MM in a mouse model. MM cells could escape rejection by losing expression of the H chain, thus giving rise to FLC MM.
ECM‐Like Adhesive Hydrogel for the Regeneration of Large Corneal Stromal Defects (Adv. Healthcare Mater. 21/2023)
Authors: Fuyan Wang, Wei Zhang, Yujie Qiao, Depeng Shi, Lizhi Hu, Jun Cheng, Jingyi Wu, Long Zhao, Donfang Li, Weiyun Shi, Lixin Xie, Qingjun Zhou
Journal: Advanced Healthcare Materials (2023)

Corneal Regeneration In article 2300192 by Lixin Xie, Qingjun Zhou, and co-workers, a photoreactive adhesive hydrogel that mimics the extracellular matrix (mainly composed of gelatin and hyaluronic acid) is designed to treat large-diameter (≥6 mm) corneal defects, which effectively promotes epithelial, stromal, and neural regeneration while preventing scar formation. It also holds great improvement and expansion potential in future applications, such as ophthalmic surgery, cell and drug delivery, tissue engineering, and 3D bioprinting.
ROS Scavenging Nanozyme Modulates Immunosuppression for Sensitized Cancer Immunotherapy (Adv. Healthcare Mater. 21/2023)
Authors: Wenjing Mo, Shujie Liu, Xiaozhi Zhao, Fayun Wei, Yuhang Li, Xinan Sheng, Wenmin Cao, Meng Ding, Wenlong Zhang, Xiaoqing Chen, Longxiyu Meng, Sheng Yao, Wenli Diao, Hui Wei, Hongqian Guo
Journal: Advanced Healthcare Materials (2023)

Nanoenzymes In article 2300191 by Wenli Diao, Hui Wei, Hongqian Guo, and co-workers, a Zr-CeO nanozyme is developed to possess enhanced activities mimicking superoxide dismutase and catalase. Via scavenging intracellular reactive oxygen species, Zr-CeO exerts remarkable effects on diminishing myeloid-derived suppressor cells and M2-TAM immunosuppression simultaneously, and eventually boosts anti-tumor immune response and sensitizes tumor immunotherapy.
Combination Therapy of Lox Inhibitor and Stimuli‐Responsive Drug for Mechanochemically Synergistic Breast Cancer Treatment (Adv. Healthcare Mater. 21/2023)
Authors: Shanshan Zhu, Tian Zhang, Huan Gao, Guorui Jin, Jin Yang, Xiaocong He, Hui Guo, Feng Xu
Journal: Advanced Healthcare Materials (2023)

Mechanochemically Synergistic Treatment In article 2300103 by Xiaocong He, Hui Guo, Feng Xu, and co-workers, a combination therapy strategy based on extracellular matrix (ECM) modulator and tumor microenvironment (TME)-responsive drug is developed for the first attempt of mechanochemically synergistic treatment of breast cancer. ECM modulation can enhance smart drug diffusion to tumor cells, while the following controlled drug release triggered by TME can reduce off-target accumulation, improving the therapeutic efficacy eventually. This work provides a promising approach for synergistic cancer treatment, especially in cancers that are associated with abnormal TME.
Engaging Adolescents in Using Online Patient Portals
Authors: Bryan A. Sisk, Alison L. Antes, Christine Bereitschaft, Madi Enloe, Sunny Lin, Meghana Srinivas, Fabienne Bourgeois, James M. DuBois
Journal: JAMA Network Open (2023)

Many health care systems offer adolescents access to health information through online patient portals, but few studies have explored how to engage adolescents in using and benefiting from online portals.To determine how US children's hospitals have attempted to encourage adolescent portal use, barriers to engaging adolescents, and ideal future goals for engagement.This qualitative study performed structured qualitative interviews with informatics administrators from children's hospitals across the US between February and July 2022. Informatics administrators were employed by US health care systems that managed a children's hospital with at least 50 dedicated pediatrics beds. Data analysis was performed from November 2022 to January 2023.This study used thematic analysis of (1) current steps that health care systems had taken to engage adolescents in using their online patient portals and (2) barriers to engaging adolescents and ideal future goals and outcomes of engagement.Among 58 total interviews with 65 informatics administrators who represented 63 hospitals across 58 health care systems, 6 themes of approaches to engaging adolescents in portal use were identified: (1) promoting and educating adolescents about portal enrollment, (2) establishing workflows to support enrollment, (3) seeking and incorporating feedback, (4) creating a culture or environment supporting engagement, (5) increasing portal utility, and (6) limited efforts. Barriers to engaging adolescents in portal use related to either (1) stakeholder investment, interest, and capabilities or (2) intersecting technical, ethical, and legal factors. Participants identified 4 ideal future efforts to engage adolescents: (1) develop adaptable private means of communication with adolescents, (2) use adolescent-centric user design, (3) enhance promotion and education about portal use, and (4) simplify and adapt workflows to encourage enrollment. Participants described 3 ideal outcomes of this future engagement: (1) provide education about current health, (2) prepare for transition to adulthood, and (3) improve digital health education of adolescents.In this qualitative study of informatics administrators, children's hospitals across the US were found to have varying degrees of efforts to engage adolescents in using their portals. Most of these efforts focused on supporting adolescent enrollment, but fewer efforts focused on making the portal useful and interesting to adolescents.
Effects of B Cell Depletion by <scp>CD19‐Targeted</scp> Chimeric Antigen Receptor T Cells in a Murine Model of Systemic Sclerosis
Authors: Jérôme Avouac, Anne Cauvet, Cindy Orvain, Morgane Boulch, Françoise Tilotta, Ly Tu, Raphaël Thuillet, Mina Ottaviani, Christophe Guignabert, Philippe Bousso, Yannick Allanore
Journal: Arthritis & Rheumatology (2023)

Objective Our goal was to study the tolerance and efficacy of two B cell depletion strategies, including one with CD19‐targeted chimeric antigen receptor (CAR) T cells, in a preclinical model mimicking the severe lung damages observed in systemic sclerosis. Methods B cell depletion strategies were evaluated in the Fra‐2 transgenic (Tg) mouse model. We considered a first group of 16 untreated mice, a second group of 15 mice receiving a single dose of anti‐CD20 monoclonal antibody (mAb), and a third group of 8 mice receiving CD19‐targeted CAR‐T cells in combination with anti‐CD20 monoclonal antibody. After six weeks of clinical evaluation, different validated markers of inflammation, lung fibrosis, and pulmonary vascular remodeling were assessed. Results CD19‐targeted CAR‐T cells infusion in combination with anti‐CD20 mAb resulted in a deeper B cell depletion than anti‐CD20 mAb alone in the peripheral blood and lesional lungs of Fra‐2 Tg mice. CAR‐T cell infusion worsened the clinical score and increased mortality in Fra‐2 Tg mice. In line with the above findings, CAR‐T cell infusion significantly increased lung collagen content, the histological fibrosis score, and right ventricular systolic pressure. CAR‐T cells accumulated in lesional lungs and promoted T activation and inflammatory cytokine production. Treatment with anti‐CD20 mAb in monotherapy had no impact on lung inflammation–driven fibrosis and pulmonary hypertension. Conclusion B cell therapies failed to show efficacy in the Fra2 Tg mice. The exacerbated Fra‐2 lung inflammatory burden stimulated accumulation and expansion of activated CD19‐targeted CAR‐T cells, secondarily inducing T cell activation and systemic inflammation, finally leading to disease worsening.
Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma
Authors: Shayan Cheraghlou, Nicole A. Doudican, Maressa C. Criscito, Mary L. Stevenson, John A. Carucci
Journal: JAMA Dermatology (2023)

Merkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably.
Using AI to measure Parkinson’s disease severity at home
Authors: Md Saiful Islam, Wasifur Rahman, Abdelrahman Abdelkader, Sangwu Lee, Phillip T. Yang, Jennifer Lynn Purks, Jamie Lynn Adams, Ruth B. Schneider, Earl Ray Dorsey, Ehsan Hoque
Journal: npj Digital Medicine (2023)

We present an artificial intelligence (AI) system to remotely assess the motor performance of individuals with Parkinson's disease (PD). In our study, 250 global participants performed a standardized motor task involving finger-tapping in front of a webcam. To establish the severity of Parkinsonian symptoms based on the finger-tapping task, three expert neurologists independently rated the recorded videos on a scale of 0-4, following the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The inter-rater reliability was excellent, with an intra-class correlation coefficient (ICC) of 0.88. We developed computer algorithms to obtain objective measurements that align with the MDS-UPDRS guideline and are strongly correlated with the neurologists' ratings. Our machine learning model trained on these measures outperformed two MDS-UPDRS certified raters, with a mean absolute error (MAE) of 0.58 points compared to the raters' average MAE of 0.83 points. However, the model performed slightly worse than the expert neurologists (0.53 MAE). The methodology can be replicated for similar motor tasks, providing the possibility of evaluating individuals with PD and other movement disorders remotely, objectively, and in areas with limited access to neurological care.
Toward Language Justice in Environmental Health Sciences in the United States: A Case for Spanish as a Language of Science
Authors: Yoshira Ornelas Van Horne, Laura M. Diaz, Jessica Trowbridge, Cecilia S. Alcala, David J.X. González
Journal: Environmental Health Perspectives (2023)

Increasingly, marginalized communities are disproportionately facing the worsening effects of environmental hazards, including air pollution, water pollution, and climate change. Language isolation and accessibility has been understudied as a determinant of health. Spanish, despite being the second-most common language in the United States with some 41.8 million speakers, has been neglected among environmental health scientists. Building capacity in high-quality Spanish-language science communication, both for scientific and nonscientific audiences, can yield improvements in health disparities research, public health literacy, international collaborations, and diversity and inclusion efforts.
Health Claims and Doses of Fish Oil Supplements in the US
Authors: Joanna N. Assadourian, Eric D. Peterson, Samuel A. McDonald, Anand Gupta, Ann Marie Navar
Journal: JAMA Cardiology (2023)

One in 5 US adults older than 60 years takes fish oil supplements often for heart health despite multiple randomized clinical trials showing no data for cardiovascular benefit for supplement-range doses. Statements on the supplement labels may influence consumer beliefs about health benefits.